1. Field of the Invention
The invention relates to the fields of molecular biology, medicine, virology and Vaccine development.
2. Description of Related Art
Vaccination is the administration of antigenic material (the vaccine) to produce immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens and are generally considered to be the most effective means of preventing infectious diseases. The material administered can for instance be live but weakened forms of pathogens (such as for instance bacteria or viruses), killed or inactivated forms of these pathogens, or purified material such as proteins.
Disadvantages of live, but weakened forms of pathogens are that these pathogens are still able to replicate and can in some cases manifest as a full-blown possibly life-threatening infection, especially in immunocompromised hosts. These forms of pathogens also have the possibility to mutate and become more virulent through such mutations. Killed or inactivated forms, if properly inactivated, do not have these disadvantages, but they have other disadvantages. Since a killed or inactivated pathogen cannot multiply, a large number of pathogens is required to stimulate immunity. Further, periodic boosters must be given to maintain immunity, only humoral immunity can be induced and since the vaccine must be injected (and not for instance orally taken), it is costly to administer.
Subunit vaccines are protein based vaccines that contain purified antigens rather than whole organisms; an example is the Bordetella pertussis antigens included in the acellular DPT vaccine. The acellular DPT vaccine comprises diphtheria and tetanus toxins and selected antigens of the pertussis pathogen. Subunit vaccines are not infectious, so they can safely be given to immunocompromised individuals, and they are less likely to induce unfavorable immune reactions that may cause side effects. Disadvantages of subunit vaccines are that the antigens may not retain their native conformation, so that antibodies produced against the subunit may not recognize the same protein on the pathogen surface. In general it takes at least two inoculations with a protein based vaccine to confer adequate protection. Another disadvantage is that isolated protein does not stimulate the immune system as well as a whole organism vaccine, because various components of live-attenuated and whole-inactivated vaccines provide co stimulatory signals.
In general, the effectiveness of subunit vaccines is increased by giving them in combination with adjuvant. Adjuvant slows antigen release for a more sustained immune stimulation, binds toll-like receptors on macrophages and dendritic cells to stimulate production of inflammatory cytokines, and activates APC to express B7. Alum (aluminum salts) is a common adjuvant used in human vaccines; it aggregates proteins to make them easier for phagocytes to engulf. Pertussis toxin, one of the components of the acellular DPT, acts as an adjuvant in that vaccine. Some bacterial components used as adjuvant in animals but which cause too much inflammation to be safe in humans are whole Mycobacterium tuberculosis, muramyl dipeptide from Mycobacterial cell walls, and bacterial DNA. One drawback of adjuvant used in human subunit vaccines is that such adjuvant induces a broad nonspecific immune response rather than a specific immune response restricted to the administered antigen.
Because the different forms of the presently available vaccines all have their specific drawbacks, there is a need for alternative vaccine strategies.